Preliminary studies have shown that lithium produces marked alterations in the levels of myo-inositol and myo-inositol l-phosphate in the cerebral cortex of experimental animals. Our preliminary objective is to determine the mechanism underlying these changes and to examine the possible effects of lithium on other compounds in this biochemical system. This will be carried out by studying effects of lithium on the levels of myo-inositol, myo-inositol l-phosphate, myo-inositol 1,2-cyclic phosphate and the phosphoinositides in various brain regions and peripheral organs following both acute and chronic administration of the drug. In addition we intend to examine the effect of lithium on the transport and synthesis of myo-inositol and on the synthesis of phosphoinositides in brain by studying the uptake and incorporation of radioactively labelled precursors. We also found in our preliminary studies that the lithium-induced alterations in myo-inositol metabolism in brain are inhibited by atropine and scopolamine. This suggests that the changes may be secondary to a stimulatory effect of lithium on cholinergic systems. To investigate this possibility studies will be conducted to determine whether drugs which are known to stimulate cholinergic transmission such as pilocarpine and physostigmine produce the same metabolic alterations as are found with lithium. Myo-inositol, myo-inositol phosphates and the phosphoinositides are important membrane constituents and this project could contribute some significant information regarding effects of lithium on metabolic processes related to membrane function. Evidence may also be obtained which will support the hypothesis that lithium influences cholinergic transmission. In addition, this research will provide data which can be used to evaluate the usefulness of lithium as a pharmacological tool in further studies of the functional role of the compounds under investigation.